Significant interactions occur at the interface between dialysis membranes and blood during every hemodialysis procedure. These interactions result in the activation of the complement system, the coagulation and the kallikrein pathways. Platelets, neutrophils and lymphocytes are also involved in this interaction. Preliminary evidence also suggests the formation of leukotrienes by activated neutrophils during dialysis. These interactions are a function of the type of dialysis membrane used, and a function of reuse of these membranes. Increasing evidence suggests that these interactions have a significant effect on the morbidity and mortality of the more than 50,000 patients on chronic hemodialysis in the United States, with consequent economic implications. The objective of this proposal is to continue the study of the blood-membrane interactions; in particular, we propose the study of the activation of the coagulation pathway, platelet activation and leukotriene production by activated neutrophils. Possible synergism in the activation of these pathways will also be studied. These interactions will also be studied in sheep animal models and will be extended to include in-vitro models, and the use (in-vitro) of specific pharmacological agents to block the activation of these pathways.